Evidence map›Paper›PMID 10523655›Full record

ArticleMolecular and cellular biology1999

Antagonistic effects of protein kinase C alpha and delta on both transformation and phospholipase D activity mediated by the epidermal growth factor receptor.

A Hornia, Z Lu, T Sukezane, M Zhong, T Joseph, P Frankel, D A Foster

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 75 citations in OpenAlex.

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  7. Protein kinase C: the "masters" of calcium and lipid.Cold Spring Harbor perspectives in biology · 2011
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

A HorniaDepartment of Biological Sciences, Hunter College of The City University of New York, New York, New York 10021, USA.
Z Lu
T Sukezane
M Zhong
T Joseph
P Frankel
D A Foster
Hunter College · USCity University of New York · US

Funding

WILD TYPE &MUTANT P53 INTERACTIONS WITH HIV LTR DNAG12RR003037 · NCRR · HUNTER COLLEGE · PI DOTTIN, ROBERT P · 1985 to 2011
$27.6M
Role of phospholipase D in tumorigenesisR01CA046677 · NCI · HUNTER COLLEGE · PI FOSTER, DAVID A · 1997 to 2014
$3.6M
BASIS FOR TRANSFORMATION BY FUJINAMI SARCOMA VIRUSR29CA046677 · NCI · HUNTER COLLEGE · PI FOSTER, DAVID A · 1989 to 1993
–
NCI NIH HHS CA46677NCI NIH HHS R01 CA046677NCRR NIH HHS G12 RR003037NCRR NIH HHS RR-03037
6 · The paper itself

Abstract

Downregulation of protein kinase C delta (PKC delta) by treatment with the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) transforms cells that overexpress the non-receptor class tyrosine kinase c-Src (Z. Lu et al., Mol. Cell. Biol. 17:3418-3428, 1997). We extended these studies to cells overexpressing a receptor class tyrosine kinase, the epidermal growth factor (EGF) receptor (EGFR cells); like c-Src, the EGF receptor is overexpressed in several human tumors. In contrast with expectations, downregulation of PKC isoforms with TPA did not transform the EGFR cells; however, treatment with EGF did transform these cells. Since TPA downregulates all phorbol ester-responsive PKC isoforms, we examined the effects of PKC delta- and PKC alpha-specific inhibitors and the expression of dominant negative mutants for both PKC delta and alpha. Consistent with a tumor-suppressing function for PKC delta, the PKC delta-specific inhibitor rottlerin and a dominant negative PKC delta mutant transformed the EGFR cells in the absence of EGF. In contrast, the PKC alpha-specific inhibitor Go6976 and expression of a dominant negative PKC alpha mutant blocked the transformed phenotype induced by both EGF and PKC delta inhibition. Interestingly, both rottlerin and EGF induced substantial increases in phospholipase D (PLD) activity, which is commonly elevated in response to mitogenic stimuli. The elevation of PLD activity in response to inhibiting PKC delta, like transformation, was dependent upon PKC alpha and restricted to the EGFR cells. These data demonstrate that PKC isoforms alpha and delta have antagonistic effects on both transformation and PLD activity and further support a tumor suppressor role for PKC delta that may be mediated by suppression of tyrosine kinase-dependent increases in PLD activity.

Indexed as

Cell Transformation, NeoplasticAcetophenonesAnimalsBenzopyransCarbazolesCells, CulturedCrosses, GeneticEpidermal Growth FactorErbB ReceptorsIndolesIsoenzymesModels, GeneticMutagenesis, InsertionalPhospholipase DProtein Kinase CProtein Kinase C-alphaAcetophenonesBenzopyransCarbazolesEpidermal Growth FactorErbB ReceptorsGo 6976IndolesIsoenzymesPhospholipase DPrkcd protein, ratProtein Kinase CProtein Kinase C-alphaProtein Kinase C-deltaRecombinant ProteinsrottlerinTetradecanoylphorbol Acetate

Identifiers

PMID10523655
PMCPMC84804
OpenAlexW2167409254

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.